Project Summary/Abstract This research is a vital part of making targeted-hyperthermia treatments for cancer therapy clinically viable. For treatment monitoring and efficacy assessment, interstitial temperature probe readings are the current standard metric. However, temperature probes are invasive, prone to infection, and provide a limited sampling of the tumor volume. Magnetic resonance temperature imaging (MRTI) has the potential to alleviate these shortcomings: (1) 3D volumetric temperature measurements can provide coverage of both the tumor volume and surrounding critical structures; (2) measurement is completely noninvasive?patient discomfort and complications due to interstitial temperature probes are eliminated. While MRTI has achieved widespread use for short-duration high-temperature ablative thermal therapies, treatment-monitoring requirements for hyperthermia are significantly different. Robustly monitoring a small temperature rise (several degrees Celsius) over a long hyperthermia treatment period (60-90 minutes) is not feasible in many anatomic locations with current techniques. Patient motion, field drift, treatment induced susceptibility change, and other systemic errors can confound MRTI. A key aim of this proposal is to develop a stable and effective MRTI technique for hyperthermia treatment monitoring in the breast. Temperature is not the only plausible metric for predicting tumor response to hyperthermia. Increased tumor oxygenation and perfusion are known to sensitize tumors to radiotherapy and chemotherapy. This proposal will develop and test the use of quantitative magnetic resonance imaging (MRI) to assess hyperthermia-induced changes in tumor oxygenation and perfusion. The overarching goal of this proposal is to accelerate the adoption of mild-hyperthermia for cancer therapy by providing non-invasive multi-parametric MRI techniques for treatment monitoring and efficacy assessment. The project consists of three specific aims to achieve this goal: 1) Develop stable, hyperthermia dedicated method for 3D temperature measurement in tissues containing aqueous and adipose tissues; 2) Develop quantitative MRI techniques to measure hyperthermia induced changes in tumor oxygenation and perfusion; 3) Evaluate developed thermometry and quantitative MRI techniques during a hyperthermia heating protocol in a preclinical tumor model. RELEVANCE TO PUBLIC HEALTH: Phase III clinical trials have demonstrated that hyperthermia when combined with radiotherapy or chemotherapy leads improves local control and/or survival for a number of cancers. Technical developments proposed in this application will accelerate the adoption of these cancer- fighting therapies by providing non-invasive techniques that are better tolerated by patients and provide superior prognostic measures and treatment monitoring capabilities. Software and techniques developed under this project will be freely shared on Github to help enable and accelerate the adoption of efficacious MRI- guided hyperthermia treatments.